title: Standardized baseline human corneal subbasal nerve density for clinical investigations with laser-scanning in vivo confocal microscopy.
abstract: OBJECTIVE
  We established a baseline value for central corneal subbasal nerve density in a large, healthy cohort.
  
  
  METHODS
  A total of 106 healthy volunteers (207 eyes) underwent full ophthalmic examination, including laser-scanning in vivo confocal microscopy (IVCM) of the central cornea. Images of the corneal subbasal nerve plexus were acquired and analyzed based on defined criteria. Nerve tracing was performed by two human observers and by a fully automated method. Subbasal nerve density was stratified by eye, observer, tracing method, calculation method, and age group. Association of nerve density with age was examined by linear regression and population distribution was examined by nonlinear regression.
  
  
  RESULTS
  We analyzed 892 distinct, high quality images of the subbasal nerve plexus (mean, 4.3 images/eye) from 207 eyes. An overall mean central subbasal nerve density of 19 mm/mm(2) was found in 106 subjects aged 15 to 88 years, independent of eye, sex, or nerve tracing method, while the SD was a consistent 4 to 5 mm/mm(2). Subbasal nerve density followed a normal Gaussian distribution, and correlated negatively with age, with a mean decline of 0.25% to 0.30% per year, independent of eye, observer, or nerve tracing method. Moreover, the use of automated tracing techniques and randomized sampling may improve the speed and reproducibility of subbasal nerve density assessment for clinical applications.
  
  
  CONCLUSIONS
  A baseline human corneal subbasal nerve density has been determined by laser-scanning IVCM using rigorous methods. The methods and results could aid in the future assessment of corneal nerves in various patient populations.
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Marlen
authors.initials: M
authors.lastname: Parissi
authors.forename: Georgios
authors.initials: G
authors.lastname: Karanis
authors.forename: Stefan
authors.initials: S
authors.lastname: Randjelovic
authors.forename: Johan
authors.initials: J
authors.lastname: Germundsson
authors.forename: Enea
authors.initials: E
authors.lastname: Poletti
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ruggeri
authors.forename: Tor Paaske
authors.initials: TP
authors.lastname: Utheim
authors.forename: Neil
authors.initials: N
authors.lastname: Lagali
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003315:Cornea / Q000294:innervation*; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008875:Middle Aged; D009882:Ophthalmic Nerve / Q000033:anatomy & histology*; D012044:Regression Analysis; D055815:Young Adult
keywords: confocal microscopy; imaging; subbasal nerve